McMurray was born in Joplin, Missouri, and began racing go-karts from childhood, competing in karting events across the country before moving to late model stock cars. He married Christy Futrell in July 2009; the couple have two children.
McMurray entered the NASCAR Craftsman Truck Series in 1999 and ran a partial schedule over two seasons before graduating to the Busch Series with Brewco Motorsports. Driving the No. 27 Williams Travel Centers Chevrolet full-time in 2001 and 2002, he won two Busch Series races in 2002 and finished sixth in points. He became the one-hundredth different driver to win in the NASCAR Grand National Series.
McMurray entered NASCAR Cup competition as an interim replacement for Sterling Marlin, who fractured a vertebra in a crash at Kansas Speedway in 2002. In just his second Cup start — and first on a non-restrictor-plate track — McMurray raced away from Bobby Labonte and Tony Stewart to win the UAW-GM Quality 500 at Charlotte Motor Speedway, leading 96 of the final 100 laps. The victory, considered one of the biggest upsets in NASCAR history, set a modern-era record for fewest starts before a first win.
McMurray joined Ganassi full-time in 2003 and won the Cup Series Rookie of the Year award. He posted 23 top-tens in 2004 and twelve top-tens in his final stretch of races that season. He left Ganassi after 2005 for Roush Racing, driving the No. 26 Crown Royal Ford from 2006 to 2009.
At Roush, McMurray won the 2007 Pepsi 400 at Daytona by a margin of 0.005 seconds over Kyle Busch, one of the closest finishes in Daytona history. He also won at Talladega in November 2009 in his final race for Roush before rejoining Chip Ganassi's merged team, now Earnhardt Ganassi Racing, in the No. 1 Chevrolet.
McMurray's 2010 season was the defining chapter of his career. On February 14 he won the Daytona 500, passing Kevin Harvick with two laps to go and holding off Greg Biffle and Dale Earnhardt Jr. In July he won the Brickyard 400 at Indianapolis Motor Speedway, joining Jimmie Johnson (2006) and Dale Jarrett (1996) as the only drivers to win both premier events in the same year. Chip Ganassi became the first owner to win the Daytona 500, Brickyard 400, and Indianapolis 500 in the same calendar year. McMurray also won the Bank of America 500 at Charlotte in October, finishing the season with three victories and fourteen in the standings.
He also won the 2015 24 Hours of Daytona with Chip Ganassi Racing alongside Tony Kanaan, Scott Dixon, and Kyle Larson, joining A.J. Foyt and Mario Andretti as the only drivers to have won both the Daytona 500 and the 24 Hours of Daytona.
McMurray remained with Ganassi through 2018. He won the All-Star Race in 2014 and took victories at Talladega in October 2013 and Charlotte in 2010. He qualified for the Cup Series playoffs in 2015, 2016, and 2017. His 2018 season was his worst since 2011, and at its end, Kurt Busch was announced as his replacement in the No. 1.
McMurray drove the No. 40 for Spire Motorsports in the 2019 Daytona 500 and returned for the 2021 race, finishing eighth — his second top-ten in the event.
Following his retirement from full-time Cup competition, McMurray joined Fox Sports as an analyst for their NASCAR broadcasts starting in 2019, appearing on NASCAR RaceDay and NASCAR Race Hub. In 2025 he joined CW Sports as a color commentator for NASCAR on The CW.
McMurray's 2010 Daytona 500–Brickyard 400 double remains one of the most distinctive single-season achievements in NASCAR's modern era. His career spanned sixteen full-time Cup seasons, two stints with Chip Ganassi Racing, and multiple wins across NASCAR's premier divisions and the 24 Hours of Daytona.